Background:Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19,we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendr...Background:Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19,we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein.Methods:Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB,and IRF were differ-entiated into macrophages over 3 days using phorbol 12-myristate 13-acetate,or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α.Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours.Results:Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein.Conclusions:Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflam-matory transcription factors upon stimulation with S-glycoprotein.BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19.Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.展开更多
文摘Background:Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19,we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein.Methods:Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB,and IRF were differ-entiated into macrophages over 3 days using phorbol 12-myristate 13-acetate,or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α.Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours.Results:Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein.Conclusions:Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflam-matory transcription factors upon stimulation with S-glycoprotein.BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19.Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.